Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. The authors conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit IPF patients experiencing an acute exacerbation (IPF-AE). Eleven critically-ill IPF patients with AEs with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Outcomes among the trial subjects were compared to those of 20 historical controls treated with glucocorticoids.

Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one historical control (left panel). Maximum walk distance increased in 4/5 treated subjects (middle panel). One-year survival of trial subjects was 46±15% vs. 0% among historical controls (right panel). Three (of four) subjects who responded to an augmented regimen of TPE together with rituximab plus IVIG were relapse-free up to 237 days. No serious adverse events were attributable to the experimental medications.

Expert CommentaryThis small trial suggests that therapies aimed at reducing autoantibodies benefit some patients with IPF-AE. Evidence of the possible contribution of autoimmune mechanisms in the pathogenesis of IPF has been accumulating in recent years. This current study by Donahoe et al provides further suggestive evidence that autoimmunity might be involved, at least in IPF-AEs. Further validation in larger groups of patients with IPF-AEs, and possibly IPF patients without an acute exacerbation should be considered.